{\lambda}-Cent-Dians and Generalized-Center for Network Design

In this paper, we extend the notions of $\lambda$-cent-dian and generalized-center from Facility Location Theory to the more intricate domain of Network Design. Our focus is on the task of designing a sub-network within a given underlying network while adhering to a budget constraint. This sub-network is intended to efficiently serve a collection of origin/destination pairs of demand. % rather than individual points. The $\lambda$-cent-dian problem studies the balance between efficiency and equity. We investigate the properties of the $\lambda$-cent-dian and generalized-center solution networks under the lens of equity, efficiency, and Pareto-optimality. We provide a mathematical formulation for $\lambda\geq 0$ and discuss the bilevel structure of this problem for $\lambda>1$. Furthermore, we describe a procedure to obtain a complete parametrization of the Pareto-optimality set based on solving two mixed integer linear formulations by introducing the concept of maximum $\lambda$-cent-dian. We evaluate the quality of the different solution concepts using some inequality measures. Finally, for $\lambda\in[0,1]$, we study the implementation of a Benders decomposition method to solve it at scale

Cucurbit [7] uril encapsulated cisplatin overcomes resistance to cisplatin induced by Rab25 overexpression in an intraperitoneal ovarian cancer model

Background Ovarian cancer is the most fatal of gynaecological malignancies, usually detected at a late stage with intraperitoneal dissemination. Appropriate preclinical models are needed that recapitulate both the histopathological and molecular features of human ovarian cancer for drug-efficacy analysis. Methods Longitudinal studies comparing cisplatin performance either alone or in a novel cisplatin-based delivery-system, cucurbit[7]uril-encapsulated cisplatin (cisplatin@CB[7]) were performed on subcutaneous (s.c.) and intraperitoneal (i.p.) xenografts using the human ovarian cancer cell line A2780 stably expressing the small GTPase Rab25, which allows A2780 intraperitoneal growth; and luciferase, to allow tumour load measurement by non-invasive bioluminescent imaging. Results Rab25 expression induced cisplatin resistance compared to the parental cell line as assessed by the MTT assay in vitro. These findings did not translate in vivo, where cisplatin resistance was determined by the microenvironment. Subcutaneous xenografts of either parental A2780 or cisplatin-resistant Rab25-expressing A2780 cells presented similar responses to cisplatin treatment. In contrast, increased cisplatin resistance was only detected in i.p. tumours. Treatment of the cisplatin-resistant i.p. model with the novel cisplatin@CB[7] delivery system resulted in a substantial reduction of i.p. tumour load and increased necrosis. Conclusions Poor clinical performance of novel chemotherapeutics might reflect inappropriate preclinical models. Here we present an ovarian i.p. model that recapitulates the histopathological and chemoresistant features of the clinical disease. In addition, we demonstrate that the novel cisplatin-delivery system, cisplatin@CB[7] may have utility in the treatment of drug-resistant ovarian human cancers

Modelling and Simulation of the Radiant Field in an Annular Heterogeneous Photoreactor Using a Four-Flux Model

This work focuses on modeling and simulating the absorption and scattering of radiation in a photocatalytic annular reactor. To achieve so, a model based on four fluxes (FFM) of radiation in cylindrical coordinates to describe the radiant field is assessed. This model allows calculating the local volumetric rate energy absorption (LVREA) profiles when the reaction space of the reactors is not a thin film. The obtained results were compared to radiation experimental data from other authors and with the results obtained by discrete ordinate method (DOM) carried out with the Heat Transfer Module of Comsol Multiphysics® 4.4. The FFM showed a good agreement with the results of Monte Carlo method (MC) and the six-flux model (SFM). Through this model, the LVREA is obtained, which is an important parameter to establish the reaction rate equation. In this study, the photocatalytic oxidation of benzyl alcohol to benzaldehyde was carried out, and the kinetic equation for this process was obtained. To perform the simulation, the commercial software COMSOL Multiphysics v. 4.4 was employed

Feelings, Stress, and Coping of Nurses Amidst COVID-19 Outbreak in Saudi Arabia

Background: A year after the COVID-19 pandemic spread around the world, the pandemic is still affecting healthcare systems with an increasing number of infected healthcare workers. Such a unique situation may often result in emotional turmoil, anxiety, depression, and fear, which could lead to resignation and burnout. The study intended to assess the feelings of nurses toward the COVID-19 outbreak; ascertain the factors that cause stress; and determine their coping strategies and factors contributing to coping. Methods: A descriptive cross-sectional design was utilized to recruit 313 nurses working in the Ministry of Health (Saudi Arabia) hospitals that accommodate COVID-19 patients. The study instrument was adapted and modified from the ”MERS-CoV Staff Questionnaire” and the Brief COPE. Results: The results showed that female, married, those with a bachelor’s degree, and aged 25–34 years had higher significant coping strategies. On the other hand, Filipino nurses assigned in the Outpatient Department and COVID-19 Isolation Ward had more negative feelings and encountered several factors causing stress but were coping in a better way than others. Conclusion: Nurses’ commitment to their profession appears to be an intrinsic motivation to continue caring for COVID-19 patients despite the risk of infection. Comfort with religion, spiritual beliefs, and the presence of a support system were the coping strategies used by nurses to ameliorate the stress and negative feelings during the COVID-19 outbreak

Protected Areas’ Latent Functions and Social Consequences: A Case from Mount Hamiguitan, Philippines

While protected areas (PAs) are established primarily for biological diversity conservation and provision of ecological services, social dimensions comes into play. This paper extends the discourse on PAs’ impact to local communities by focusing on the latent functions and social consequences utilizing Robert Merton’s Functional Analysis. Based on in-depth interviews among community leaders and elders, and forest custodians around Mount Hamiguitan, a UNESCO World Heritage Site, it is revealed that establishment of PAs entails varied consequences beyond what are being intended and manifested. While communities availed of some latent benefits from the declaration of the PA, they also have responses that limit the success of conservation initiatives. Hence, forest protection is a complex social and political process that demands more integrative response on community’s social, cultural, and political structures and dynamics

Innate immunity in ocular Chlamydia trachomatis infection: contribution of IL8 and CSF2 gene variants to risk of trachomatous scarring in Gambians

BACKGROUND: Trachoma, a chronic keratoconjunctivitis caused by Chlamydia trachomatis, is the world's commonest infectious cause of blindness. Blindness is due to progressive scarring of the conjunctiva (trachomatous scarring) leading to in-turning of eyelashes (trichiasis) and corneal opacification. We evaluated the contribution of genetic variation across the chemokine and cytokine clusters in chromosomes 4q and 5q31 respectively to risk of scarring trachoma and trichiasis in a large case-control association study in a Gambian population. METHODS: Linkage disequilibrium (LD) mapping was used to investigate risk effects across the 4q and 5q31 cytokine clusters in relation to the risk of scarring sequelae of ocular Ct infection. Disease association and epistatic effects were assessed in a population based study of 651 case-control pairs by conditional logistic regression (CLR) analyses. RESULTS: LD mapping suggested that genetic effects on risk within these regions mapped to the pro-inflammatory innate immune genes interleukin 8 (IL8) and granulocyte-macrophage colony stimulatory factor (CSF2) loci. The IL8-251 rare allele (IL8-251 TT) was associated with protection from scarring trachoma (OR = 0.29 p = 0.027). The intronic CSF2_27348 A allele in chromosome 5q31 was associated with dose dependent protection from trichiasis, with each copy of the allele reducing risk by 37% (p = 0.005). There was evidence of epistasis, with effects at IL8 and CSF2 loci interacting with those previously reported at the MMP9 locus, a gene acting downstream to IL8 and CSF2 in the inflammatory cascade. CONCLUSION: innate immune response SNP-haplotypes are linked to ocular Ct sequelae. This work illustrates the first example of epistatic effects of two genes on trachoma

Immunotherapy of Brain Cancers: The Past, the Present, and Future Directions

Treatment of brain cancers, especially high grade gliomas (WHO stage III and IV) is slowly making progress, but not as fast as medical researchers and the patients would like. Immunotherapy offers the opportunity to allow the patient's own immune system a chance to help eliminate the cancer. Immunotherapy's strength is that it efficiently treats relatively small tumors in experimental animal models. For some patients, immunotherapy has worked for them while not showing long-term toxicity. In this paper, we will trace the history of immunotherapy for brain cancers. We will also highlight some of the possible directions that this field may be taking in the immediate future for improving this therapeutic option